The effects of acute and chronic microwave radiation exposure [2.45 GHz, continuous wave (CW) and pulsed wave (PW)] on the blood-brain barrier (BBB) structure/function characteristics (permeability) will be studied to determine possible mechanisms by which its integrity has been altered. The changes in BBB function will be measured by using: sensitive pharmacologic assay systems (agonist/antagonist-pA2 values); generalized BBB permeability assay systems (brain uptake (BUI) technique, permeability x area (PA) product technique, intracerebral dialysis (extracellular compartment technique); tight-injunction integrity/pinocytotic activity (histologic/fluorescent techniques - La3+, horseradish peroxidaze (HRP), ferritin, rhodamine-ferritin complex) using electron microscopy (EM) and fluorometric assays. Since most of these studies are to be conducted at "non-thermal" exposure levels of microwave radiation, extensive dosimetry studies will be conducted, particularly emphasizing the apparent increased susceptibility of the BBB to permeability changes produced by pulsed wave (PW) microwave radiation. The possibility that secondary or associated mechanism of microwave energy absorption are responsible for the observed changes in BBB permeability characteristics will be investigated. Change in cerebral blood flow will be evaluated for possible effects on the assay systems employed in our studies. Some of the effects of "non-thermal" microwave radiation effect on other vascular systems suggested that free- radical formation may be associated with subsequent tissue damage. As a result, the possibility that free-radical formation may be associated with changes in BBB permeability will be investigated using electron spin resonance (ESR) techniques (spin trapping and spin stabilization), lipid peroxidation assays, and free-radical scavenging techniques (superoxide dismutase-SOD, vitamin C and E). These studies will provide mechanistic information of critical significance to understanding the possible deleterious effects of microwave radiation during environmental and occupational exposures.